Modulation of Second Messenger Signaling in the Brain Through PDE4 and PDE5 Inhibition: Therapeutic Implications for Neurological Disorders
Phosphodiesterase (PDE) enzymes regulate intracellular signaling pathways crucial for brain development and the pathophysiology of neurological disorders. Among the 11 PDE subtypes, PDE4 and PDE5 are particularly significant due to their regulation of cyclic adenosine monophosphate (cAMP) and cyclic...
Saved in:
| Main Authors: | , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2025-01-01
|
| Series: | Cells |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2073-4409/14/2/86 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1832588836212834304 |
|---|---|
| author | Min Kyu Park Hyun Wook Yang Seo Young Woo Dong Yeon Kim Dae-Soon Son Bo Young Choi Sang Won Suh |
| author_facet | Min Kyu Park Hyun Wook Yang Seo Young Woo Dong Yeon Kim Dae-Soon Son Bo Young Choi Sang Won Suh |
| author_sort | Min Kyu Park |
| collection | DOAJ |
| description | Phosphodiesterase (PDE) enzymes regulate intracellular signaling pathways crucial for brain development and the pathophysiology of neurological disorders. Among the 11 PDE subtypes, PDE4 and PDE5 are particularly significant due to their regulation of cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP) signaling, respectively, which are vital for learning, memory, and neuroprotection. This review synthesizes current evidence on the roles of PDE4 and PDE5 in neurological health and disease, focusing on their regulation of second messenger pathways and their implications for brain function. Elevated PDE4 activity impairs synaptic plasticity by reducing cAMP levels and protein kinase A (PKA) activity, contributing to cognitive decline, acute brain injuries, and neuropsychiatric conditions such as bipolar disorder and schizophrenia. Similarly, PDE5 dysregulation disrupts nitric oxide (NO) signaling and protein kinase G (PKG) pathways, which are involved in cerebrovascular homeostasis, recovery after ischemic events, and neurodegenerative processes in Alzheimer’s, Parkinson’s, and Huntington’s diseases. PDE4 and PDE5 are promising therapeutic targets for neurological disorders. Pharmacological modulation of these enzymes offers potential to enhance cognitive function and mitigate pathological mechanisms underlying brain injuries, neurodegenerative diseases, and psychiatric disorders. Further research into the regulation of PDE4 and PDE5 will advance therapeutic strategies for these conditions. |
| format | Article |
| id | doaj-art-558033a8b0454b84a8ac586ae8e3bd13 |
| institution | Kabale University |
| issn | 2073-4409 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cells |
| spelling | doaj-art-558033a8b0454b84a8ac586ae8e3bd132025-01-24T13:26:37ZengMDPI AGCells2073-44092025-01-011428610.3390/cells14020086Modulation of Second Messenger Signaling in the Brain Through PDE4 and PDE5 Inhibition: Therapeutic Implications for Neurological DisordersMin Kyu Park0Hyun Wook Yang1Seo Young Woo2Dong Yeon Kim3Dae-Soon Son4Bo Young Choi5Sang Won Suh6Department of Physiology, College of Medicine, Hallym University, Chuncheon 24252, Republic of KoreaDepartment of Physiology, College of Medicine, Hallym University, Chuncheon 24252, Republic of KoreaDepartment of Physiology, College of Medicine, Hallym University, Chuncheon 24252, Republic of KoreaDepartment of Physiology, College of Medicine, Hallym University, Chuncheon 24252, Republic of KoreaDivision of Data Science, Data Science Convergence Research Center, Hallym University, Chuncheon 24252, Republic of KoreaInstitute of Sport Science, Hallym University, Chuncheon 24252, Republic of KoreaDepartment of Physiology, College of Medicine, Hallym University, Chuncheon 24252, Republic of KoreaPhosphodiesterase (PDE) enzymes regulate intracellular signaling pathways crucial for brain development and the pathophysiology of neurological disorders. Among the 11 PDE subtypes, PDE4 and PDE5 are particularly significant due to their regulation of cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP) signaling, respectively, which are vital for learning, memory, and neuroprotection. This review synthesizes current evidence on the roles of PDE4 and PDE5 in neurological health and disease, focusing on their regulation of second messenger pathways and their implications for brain function. Elevated PDE4 activity impairs synaptic plasticity by reducing cAMP levels and protein kinase A (PKA) activity, contributing to cognitive decline, acute brain injuries, and neuropsychiatric conditions such as bipolar disorder and schizophrenia. Similarly, PDE5 dysregulation disrupts nitric oxide (NO) signaling and protein kinase G (PKG) pathways, which are involved in cerebrovascular homeostasis, recovery after ischemic events, and neurodegenerative processes in Alzheimer’s, Parkinson’s, and Huntington’s diseases. PDE4 and PDE5 are promising therapeutic targets for neurological disorders. Pharmacological modulation of these enzymes offers potential to enhance cognitive function and mitigate pathological mechanisms underlying brain injuries, neurodegenerative diseases, and psychiatric disorders. Further research into the regulation of PDE4 and PDE5 will advance therapeutic strategies for these conditions.https://www.mdpi.com/2073-4409/14/2/86phosphodiesterase (PDE)phosphodiesterase 4 (PDE4)phosphodiesterase 5 (PDE5)protein kinase A (PKA)protein kinase G (PKG) |
| spellingShingle | Min Kyu Park Hyun Wook Yang Seo Young Woo Dong Yeon Kim Dae-Soon Son Bo Young Choi Sang Won Suh Modulation of Second Messenger Signaling in the Brain Through PDE4 and PDE5 Inhibition: Therapeutic Implications for Neurological Disorders Cells phosphodiesterase (PDE) phosphodiesterase 4 (PDE4) phosphodiesterase 5 (PDE5) protein kinase A (PKA) protein kinase G (PKG) |
| title | Modulation of Second Messenger Signaling in the Brain Through PDE4 and PDE5 Inhibition: Therapeutic Implications for Neurological Disorders |
| title_full | Modulation of Second Messenger Signaling in the Brain Through PDE4 and PDE5 Inhibition: Therapeutic Implications for Neurological Disorders |
| title_fullStr | Modulation of Second Messenger Signaling in the Brain Through PDE4 and PDE5 Inhibition: Therapeutic Implications for Neurological Disorders |
| title_full_unstemmed | Modulation of Second Messenger Signaling in the Brain Through PDE4 and PDE5 Inhibition: Therapeutic Implications for Neurological Disorders |
| title_short | Modulation of Second Messenger Signaling in the Brain Through PDE4 and PDE5 Inhibition: Therapeutic Implications for Neurological Disorders |
| title_sort | modulation of second messenger signaling in the brain through pde4 and pde5 inhibition therapeutic implications for neurological disorders |
| topic | phosphodiesterase (PDE) phosphodiesterase 4 (PDE4) phosphodiesterase 5 (PDE5) protein kinase A (PKA) protein kinase G (PKG) |
| url | https://www.mdpi.com/2073-4409/14/2/86 |
| work_keys_str_mv | AT minkyupark modulationofsecondmessengersignalinginthebrainthroughpde4andpde5inhibitiontherapeuticimplicationsforneurologicaldisorders AT hyunwookyang modulationofsecondmessengersignalinginthebrainthroughpde4andpde5inhibitiontherapeuticimplicationsforneurologicaldisorders AT seoyoungwoo modulationofsecondmessengersignalinginthebrainthroughpde4andpde5inhibitiontherapeuticimplicationsforneurologicaldisorders AT dongyeonkim modulationofsecondmessengersignalinginthebrainthroughpde4andpde5inhibitiontherapeuticimplicationsforneurologicaldisorders AT daesoonson modulationofsecondmessengersignalinginthebrainthroughpde4andpde5inhibitiontherapeuticimplicationsforneurologicaldisorders AT boyoungchoi modulationofsecondmessengersignalinginthebrainthroughpde4andpde5inhibitiontherapeuticimplicationsforneurologicaldisorders AT sangwonsuh modulationofsecondmessengersignalinginthebrainthroughpde4andpde5inhibitiontherapeuticimplicationsforneurologicaldisorders |